The overall goals of the proposed research are to elucidate the origin of pandemic influenza viruses and the molecular basis of genetic variation. Monoclonal antibodies to each of the gene products of influenza A viruses are being prepared and used in conjunction with peptide mapping and sequence analysis to relate changes in the genes and gene products to changes in antigenicity and function. Analysis of the hemagglutinin molecule with monoclonal antibodies suggests that there are at least three nonoverlapping antigenic determinants and these can be related to changes in primary amino acid sequence. At this time, it is not known which changes are important in determining an epidemiologically significant strain of influenza virus.